title: Cell fate conversion by conditionally switching the signal-transducing domain of signalobodies.
abstract: Conditionally and strictly controlling cell fates is important for biomedical applications including cell therapies. Although previous studies have been based on regulating the expression or activation of signaling molecules, the techniques therein require improvement in terms of reducing leakiness and complexity. In this study, we propose a novel cell fate converting system using our previously developed antibody/receptor chimeras named "signalobodies" in combination with a Cre/loxP recombination system. We designed a "switch vector" where a growth signalobody gene was flanked by two loxP sites and a death signalobody gene was placed downstream of the floxed cassette. Cells transduced with the switch vector showed superior growth activity in the presence of a specific antigen. Subsequent expression of Cre induced the death signalobody, leading to conditional cell death. This technology could be applicable for other cell fate conversion systems including differentiation and migration, by using appropriate signal-transducing domains.
authors.affiliation: Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tone
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawahara
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Nagamune
mesh_terms: D000906:Antibodies / Q000235:genetics / Q000378:metabolism*; D002468:Cell Physiological Phenomena; D002470:Cell Survival / Q000187:drug effects; D003584:Cytological Techniques / Q000379:methods*; D006801:Humans; D019426:Integrases; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000906:Antibodies; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C045073:Cre recombinase; D019426:Integrases
keywords: Cre recombinase; antibody; cell fate; chimeric protein; receptor; signal transduction